Myxovirus Resistance Protein A in Interferon-β Therapy in Patients with Multiple Sclerosis and Treatment Effectiveness Monitoring Algorithm

Czech version

Authors: J. Libertínová ¹; E. Meluzínová ¹; E. Havrdová ²; D. Horáková ² ; I. Kovářová ²; E. Hynčicová ¹; P. Lišková ¹; E. Houžvičková ¹; V. Maťoška ³; M. Zajac ⁴; A. Tomek ¹; M. Bojar ¹; P. Marusič ¹
Authors‘ workplace: Neurologická klinika 2. LF UK a FN v Motole, Praha ¹; Neurologická klinika a Centrum klinických neurověd, 1. LF UK a VFN v Praze ²; Laboratoř molekulární diagnostiky, Nemocnice Na Homolce, Praha ³; Ústav lékařské mikrobiologie, 2. LF UK a FN v Motole, Praha ⁴
Published in: Cesk Slov Neurol N 2016; 79/112(5): 547-551
Category: Original Paper

Overview

Introduction:
Interferon-β (IFNβ) is the first-line treatment for relapsing-remitting multiple sclerosis. Myxovirus resistance protein A (MxA) is considered to be an IFNß bioactivity marker. Responsiveness to the IFNß treatment may be reduced by neutralizing antibodies (NAbs).

Material and methods:
We investigated the presence of NAbs and mRNA MxA expression in a group of patients who had started IFNß treatment. mRNA MxA was measured with real-time PCR every three months. MxA induction was performed in patients in whom continuous decline was detected. NAbs were determined using the cytopathic effect method every six months. Patients were regularly observed clinically and with MRI.

Results:
119 patients were included, 99 completed the observation period of 24 months. NAbs positivity was observed in 17 patients, mostly in month 12 and 18. NAbs positivity was permanent in ten patients (10%). Nabs titre of 20–100 TRU/ml was associated with a decline in MxA levels under the cut-off in 85% of cases, and in all patients when Nabs titre exceeded 100 TRU/ml. Permanent MxA decline was seen in 19 patients – in all 10 patients with permanent NAbs positivity, in three patients with transitional NAbs positivity and in six patients without NAbs. The MxA induction was insufficient in all permanent NAbs positive patients and in two patients with isolated MxA decrease and without NAbs. MxA decrease preceded NAbs positivity in 40% of cases.

Conclusion:
MxA becomes the main laboratory marker of IFNβ efficacy as it can indicate patients at risk of IFNβ efficacy loss, even in situations when patients produce NAbs. MxA induction is necessary to verify IFNβ efficacy.

Key words:
interferon-β –MxA induction test – myxovirus resistance protein A – neutralising antibodies – multiple sclerosis

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

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